Rafi Kopelan, 10, has epidermolysis bullosa, which causes painful blisters of the skin and mucous membranes. Her father, Brett, is at right.

Courtesy of Brett Kopelan

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Originally published on November 13, 2017 4:10 pm

A child who was on the verge of death from a rare inherited disease has been treated with genetically engineered skin cells that replaced most of the skin on his body.

The treatment represents a notable success for the field of gene therapy, which has suffered many setbacks. And it's potentially good news for children suffering from a painful and often deadly skin condition called epidermolysis bullosa.

In this disease, children are born with a flawed gene that prevents the outer layer of the skin, the epidermis, from binding to the inner layer. This can cause excruciating blisters to form all over these children's bodies.

In the case in Europe, a 7-year old boy ended up in the hospital back in 2015 after 60 percent of his epidermis had sloughed off. Tobias Rothoeft, a surgeon at a burn unit at Ruhr University in Bochum, Germany, says he and his colleagues tried everything — including a skin transplant from the boy's father — to no avail.

"After nearly two months we were absolutely sure there was nothing we could do for this kid and that he would die," Rothoeft said in a telephone news conference hosted by Nature, which published the study online Wednesday.

Rothoeft and his colleagues took one last look around the medical literature and learned of researchers in Italy who were experimenting with a new treatment for this disease. Michele De Luca and colleagues at the University of Modena and Reggio Emilia were genetically engineering skin cells to repair the inborn flaw.

De Luca used a virus to insert a healthy gene into cells taken from the boy's skin. Some of those cells, stem cells, multiply indefinitely. So De Luca was able to grow entire sheets of engineered epidermis, which were shipped to the hospital in Germany.

De Luca had used this procedure successfully in 2006 to replace a relatively small patch of skin on another patient. But this boy needed to have 80 percent of his skin replaced with grafts of this genetically modified material. It took two operations, both in the fall of 2015.

"In the first one, we grafted all four limbs," De Luca told reporters in the press call. "In the second operation we grafted the remaining part of the body, mainly the back."

After eight months in the intensive care unit, the boy was well enough to go home. And, two years later, he is in school, even playing soccer.

"The kid is doing quite well," Rothoeft said. "The skin is of good quality, it doesn't need any ointments or stuff like that. It's perfectly smooth and it is quite stable. And if he gets any bruises, they just heal like bruises in every other kid."

One lingering question is the concern that gene therapies like this, involving viruses, can increase the risk of cancer. That's because the viruses insert the new gene randomly into human DNA. An attempt at using gene therapy to treat severe combined immuneodeficiency (SCID) in 2002 ended up triggering cancer in some patients.

That bad result set back the field of gene therapy, though there have since been successes treating SCID, and most recently, cancer.

"Certainly it is a potential problem," De Luca said. But he generated hundreds of millions of cells during this procedure and didn't see anything of concern. And in this case, clearly the benefits of treating the boy outweighed the risks.

News of this is just starting to trickle out to advocates who have children with epidermolysis bullosa.

"I think it's groundbreaking," says Brett Kopelan, who heads a U.S. organization focused on this disease, known by its acronym, debra. "I think it's incredibly exciting."

His 10-year-old daughter Rafi has a severe case.

"Imagine the last time you had a paper cut and you put some Purell on it and it stung, right?" Kopelan says. "Now imagine that being 60 percent of your body.

"When you have to do a bath and bandage change every day, you are subjected to severe torture. It's incredibly painful, and it can take up to 3 to 4 hours a day," he says. "As a parent, there's not a day that goes by that a little bit of my heart doesn't break.

"Yet Rafi, knowing that it's going to be an incredibly painful couple of hours, walks into the bath and bandage room ... so that we can clean her wounds to make sure they don't get infected and to prevent a potentially life-threatening situation.

"She's the bravest person I know."

In addition to the painful blisters, Rafi needs frequent throat surgeries, because her condition also affects mucous membranes. She often uses a wheelchair because it's so painful to walk.

"My daughter would love to be able to not have to wear bandages on a daily basis, she'd love to jump in a pool without worrying about it hurting, or taking a shower — or even wearing shoes."

The skin therapy described in the Nature paper wouldn't cure her — in fact, it targets a different genetic defect that causes the same condition. But a similar approach could reduce the agony of daily living. And Kopelan says medical interest in this disease is now growing rapidly.

"We've gone from zero biotechnology and pharmaceutical [companies] to like 12 companies, so we're really at an inflection point right now," he says.

Experimental treatments are getting under way in the United States and Asia, as well as in Europe. Peter Marinkovich, Jean Tang and colleagues at the Stanford University School of Medicine are using the same approach as De Luca, and they have treated seven children using smaller patches of skin.

Marinkovich tells Shots that their long-term goal is to treat a child's entire body, and the research is gradually laying the groundwork to do that. The severely injured child in Germany offered a unique opportunity to try that, and the encouraging results are generating more enthusiasm. "I was super impressed when I saw [the] results," Marinkovich says.

We're going to hear now how doctors in Europe used genetically engineered skin cells to treat a child who was on the verge of death from a rare inherited disease. The treatment represents a notable success for the field of gene therapy, which has suffered many setbacks. And it's potentially good news for children with this painful and often deadly skin condition. NPR's Richard Harris has the story.

RICHARD HARRIS, BYLINE: The boy was born with a genetic flaw that left him with a condition called junctional epidermolysis bullosa. The outer layer of his skin didn't bind well to the inner layer, and as a result, excruciating blisters appeared all over his body. In 2015, the 7-year-old boy ended up in a hospital after 60 percent of the outer layer of his skin, his epidermis, had sloughed off. Tobias Rothoeft, a surgeon at a burn unit in Bochum, Germany, says doctors tried everything, including a skin transplant from the boy's father. But nothing helped.

TOBIAS ROTHOEFT: After nearly two months, we were absolutely sure that we could do nothing for this kid and that he would die.

HARRIS: Rothoeft and his colleagues took one last look around the medical literature and learned of an Italian team that was experimenting with a new treatment for this disease. Michele De Luca at the University of Modena was genetically engineering skin cells to repair the inborn flaw.

ROTHOEFT: And he promised us he could give us enough skin to heal this kid.

HARRIS: In a phone press conference hosted by the journal Nature, De Luca explained that he used a virus to insert a healthy gene into cells taken from the boy's skin. Some of those cells - stem cells - multiply indefinitely. So De Luca was able to grow entire sheets of engineered epidermis.

(SOUNDBITE OF PRESS CONFERENCE)

MICHELE DE LUCA: They are then packaged and transferred to the hospital where they are applied.

HARRIS: De Luca used this procedure successfully 12 years ago to replace a relatively small patch of skin. But this boy needed to have 80 percent of his skin replaced with grafts of this genetically modified material. It took two operations both in the fall of 2015, starting with his arms and legs.

(SOUNDBITE OF PRESS CONFERENCE)

DE LUCA: In the first one, we grafted all four limbs. In the second operation, we grafted the remaining part of the body, mainly the back.

HARRIS: After eight months in the intensive care unit, the boy was well enough to go home. And two years later, the grafts are still going strong. Tobias Rothoeft says the boy is in school, even playing soccer.

ROTHOEFT: The kid is doing quite well. The skin is of good quality. It doesn't need any ointments or stuff like that. It's perfectly smooth, and it's quite stable. If he gets any bruises like small kids have, they just heal like bruises in every other kid do.

HARRIS: One lingering question is the concern that gene therapies like this involving viruses can increase the risk of cancer.

(SOUNDBITE OF PRESS CONFERENCE)

DE LUCA: Certainly it is a potential problem.

HARRIS: But Dr. de Luca says the risk is small compared with the life-saving benefit of this treatment. News of this is just starting to trickle out to advocates who have children with epidermolysis bullosa.

HARRIS: Brett Kopelan heads a U.S. organization focused on this disease known by its acronym DEBRA. His 10-year-old daughter, Rafi, has a severe case of the disease requiring frequent throat surgeries and the use of a wheelchair. The skin therapy described in the Nature paper wouldn't cure her, but it could reduce the agony of daily living. And Kopelan says medical interest in this disease is now growing rapidly.

KOPELAN: We've gone from zero biotechnology and pharmaceutical to 12 companies. So we're really at an inflection point right now.

HARRIS: Experimental treatments are getting underway in the United States and Asia as well as in Europe. Richard Harris, NPR News. Transcript provided by NPR, Copyright NPR.